The Strength of the Evidence Apparently Linking Periodontitis to Alzheimer’s Disease Surprised Researchers

Tuesday, January 08, 2019

Science

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By Emma Yasinski

A recent study in the scientific journal PLOS ONE suggests that the most common dementia, Alzheimer’s disease, may be caused by gum disease – in mice at least.

“The primary message is that periodontitis and/or a periodontal pathogen have systemic effects in distant organs including the brain,” Keiko Watanabe, DDS, MS, PhD, corresponding author on the study, told Incisor, “The development of amyloid plaque in mice administered a periodontal pathogen was unexpected.”

Researcher Dr. Keiko Watanabe, DDS, MS, PhD

Dr. Watanabe, who has been teaching periodontics since 1986, is Director of Post Graduate Research in Periodontics at the College of Dentistry, University of Illinois at Chicago.

Alzheimer’s disease is a devastating degenerative neurological disorder that impacts nearly six million Americans. It is characterized by the loss of short-term memories progressing toward the loss of older memories and day-to-day function over the course of years. There is currently no cure for the disease, and existing treatments are only able to slow the progression. Pharmaceutical companies have spent billions of dollars searching and testing potential cures, thus far to no avail.

Scientists do not know the precise cause of Alzheimer’s disease. What they do know, is that it begins in an area of the brain called the hippocampus – a small, seahorse-shaped region in the center of the brain responsible for encoding short-term memories. Post-mortem analyses of Alzheimer’s patients show that patients have plaques – gummed up balls of biological materials that interfere with communication between brain cells which begin forming in the hippocampus and spread outward as the disease progresses. These plaques are made up of a variety of cells, proteins, and other “gunk,” but their main ingredient is a protein called beta-amyloid 42. Another protein called phosphorylated tau, builds up and seems to shrivel cellular connections from the inside.

Many Hypotheses

As with many diseases, Alzheimer’s is also associated with increased inflammation in the brain.

There are many hypotheses as to why some individuals develop the disease as they age and others don’t, but a popular theory is that it might be instigated by viral or bacterial infections. Along with inflammation throughout the brain, much of the material found in amyloid plaques is involved in immunological responses.

In each example, the periodontitis mice showed signs of the neurological disease, while the controls did not.

Previous epidemiological research has suggested a correlation between periodontitis, also known as gum disease, and Alzheimer’s. Some post-mortem analyses have found evidence of the bacteria that cause periodontitis in Alzheimer’s patients’ brains, but not in the brains of unaffected individuals.

About 50 percent of people experience periodontitis, a bacterial infection that affects the gums, and it is even more common as patients age. The disease can lead to inflammation and tooth loss if left untreated.

Rather than being caused by the bacteria itself, the damage to patients’ bones and gums is a result of an “exuberant host immunological response to periodontal pathogens,” the study authors wrote. While studies have suggested previously that periodontitis may be a risk factor for Alzheimer’s, Dr. Watanabe and her team suspected it may be a direct cause.

The study’s authors suggest that the bacteria associated with periodontitis may travel to other areas of the body, including the brain.

“We did not expect that the periodontal pathogen would have this much influence on the brain, or that the effects would so thoroughly resemble Alzheimer’s disease.”

“Notably, regular mastication, brushing, and flossing can expose the host to bacterial products via bacteremias repeatedly throughout life, and bacteremias increase with [the] severity of the periodontitis. Thus, periodontitis may result in repeated exposure of distant organs such as the brain, liver, and pancreas to bacteria and their products,” they wrote.

Since it would be unethical to expose humans to chronic gum disease and then test their brains for signs of Alzheimer’s, Dr. Watanabe and her team studied mice. Over the course of 22 weeks, the team repeatedly applied the bacteria responsible for periodontitis to the teeth of ten mice. Another ten mice received a placebo application. They confirmed that the mice that were exposed to the pathogen experienced periodontitis by evaluating the loss of base bone that supports the teeth.

Next, the team sacrificed the mice and examined their hippocampi. They compared the two groups for several signs of Alzheimer’s disease, including degenerating neurons, beta-amyloid 42 accumulation, the presence of phosphorylated tau proteins, and inflammatory cytokines. In each example, the periodontitis mice showed signs of the neurological disease, while the controls did not.

While Dr. Watanabe expected to see the bacteria produce some evidence of Alzheimer-like pathology in the mice, she was shocked at the dramatic extent. “This was a big surprise,” Dr. Watanabe told Psych Central. “We did not expect that the periodontal pathogen would have this much influence on the brain, or that the effects would so thoroughly resemble Alzheimer’s disease.”

Next, the team is working to understand the mechanism through which periodontal bacteria may affect the brain: It is unclear whether it is a direct effect of the pathogen or possibly due to other factors it triggers.

Either way, the study provides more evidence of the importance of oral hygiene in caring for the whole health of an individual.

Author: Contributing writer Emma Yasinski received her Master of Science (MS) in science and medical journalism from Boston University. Her articles have also appeared at TheAtlantic.com, Kaiser Health News, NPR Shots, and Genetic Engineering and Biotechnology News.

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